MECHANISMS OF ANGIOTENSIN-INDUCED HYPOTENSION AND BRADYCARDIA IN THE MEDIAL SOLITARY TRACT NUCLEUS

The selective angiotensin (ANG) II antagonists losartan (AT(1)) and CG P-42112A (AT(2)) were used to determine the receptor subtype and neuro nal pathways that mediate the hypotension and bradycardia produced by 200 fmol of ANG II microinjected into the dorsal medial nucleus tractu s solitarii (NTS) or dorsal motor nucleus of the vagus (dmnX) in anest hetized rats. At dorsal medial NTS sites (0.3 mm below the surface) wh ere L-glutamate microinjections produced maximal decreases in mean art erial pressure (MAP) and heart rate (HR), ANG II (200 fmol, 50 nl, n = 16) elicited hypotension (-22 +/- 1 mmHg) and bradycardia (-26 +/- 2 beats/min). Although L-glutamate also suppressed respiration, ANG II i njections in the medial NTS did not alter respiration. Losartan inject ed at the medial NTS site caused a dose-dependent reduction of ANG II- induced decreases in MAP and HR. At 2 pmol, the AT(1) antagonist atten uated the responses to ANG II, whereas 100 pmol abolished the effects of ANG II microinjections. In contrast, the AT(2) antagonist CGP-42112 A (100 pmol) had no effect on the responses to ANG II. Neither ANG II antagonist altered the cardiovascular effects of L-glutamate injection s. Losartan injected into the dmnX blocked hypotension and bradycardia produced by ANG II at that site but did not prevent responses to subs equent ANG II injections in the medial NTS. These observations reveal that the bradycardia and hypotension evoked by ANG II in the dorsal me dulla are mediated by the AT(1)-receptor subtype and establish that th e cardioinhibitory effects of ANG II in the dorsal medial NTS are medi ated by neuronal mechanisms originating within the NTS rather than by diffusion of the peptide into the underlying dmnX.